Regulation of alternative splicing during neural development

• Project/Area Number: 23790218
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Oita University
• Principal Investigator: TOKUNAGA Akinori 大分大学, 全学研究推進機構, 助教 (70549451)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 神経発生 / RNA splicing / 発生工学 / 神経幹細胞 / RNAスプライシング / NMD / 脳・神経

Research Abstract

The functional coupling roles of alternative splicing and nonsense mediated mRNA decay in the developing brain had remained unclear. Therefore we generated conditional KO mouse of splicing regulatory factor PTB. We found that a loss of PTB caused serious hydrocephalus. PTB was expressed in neural stem cells and required for the maintenance of the adhesion structure of Radial glia formed in the ventricular zone, and the undifferentiated state.Furthermore, we generated UPF1 conditional KO mouse and found that UPF1 is essential for cell proliferation and neuronal differentiation.

Research Products

• [Journal Article] PTB deficiency causes the loss of adherens junctions in the dorsal telencehalon and leads to lethal (2013)
  • Author(s): 柴嵜孝幸
  • Journal Title: Cerebral Cortex Volume: 一(掲載予定) Issue: 8 Pages: 1-12
  • DOI: 10.1093/cercor/bhs161
  • Peer Reviewed
• [Journal Article] PTB Deficiency Causes the Loss of Adherens Junctions in the Dorsal Telencephalon and Leads to Lethal Hydrocephalus (2012)
  • Author(s): Shibasaki T, Tokunaga A, Sakamoto R, Sagara H, Noguchi S, Sasaoka T, Yoshida N
  • Journal Title: Cereb Cortex. [Epub ahead of print]
  • Peer Reviewed
• [Journal Article] Botch Promotes Neurogenesis by Antagonizing Notch. (2012)
  • Author(s): Chi Z, Zhang J, Tokunaga A, Harraz MM, Byrne ST, Dolinko A, Xu J, Blackshaw S, Gaiano N, Dawson TM, Dawson VL.
  • Journal Title: Dev Cell. Volume: 22(4) Issue: 4 Pages: 707-720
  • DOI: 10.1016/j.devcel.2012.02.011
  • Peer Reviewed
• [Journal Article] Polypyrimidine tract-binding protein regulates the cell cycle through IRES-dependent translation of CDK11(p58) in mouse embryonic stem cells (2011)
  • Author(s): Ohno S, Shibayama M, Sato M, Tokunaga A, Yoshida N
  • Journal Title: Cell Cycle. 1 Volume: 10(21) Pages: 3706-3713
  • Peer Reviewed
• [Journal Article] Fbxl10/Kdm2b deficiency accelerates neural progenitor cell death and leads to exencephaly (2011)
  • Author(s): Fukuda T, Tokunaga A, Sakamoto R, Yoshida N
  • Journal Title: Mol Cell Neurosci Volume: 46(3) Pages: 614-624
  • Peer Reviewed
• [Journal Article] Polypyrimidine tract-binding protein regulates the cell cycle through IRES-dependent translation of CDK11(p58) in mouse embryonic stem cells (2011)
  • Author(s): Ohno S, Shibayama M, Sato M, Tokunaga A, Yoshida N
  • Journal Title: Cell Cycle Volume: 10(21) Issue: 21 Pages: 3706-3713
  • DOI: 10.4161/cc.10.21.17903
  • Peer Reviewed
• [Journal Article] N.Fbxl10/Kdm2b deficiency accelerates neural progenitor cell death and leads to exencephaly. (2011)
  • Author(s): Fukuda, T., Tokunaga, A., Sakamoto, R., Yoshida
  • Journal Title: Molecular and cellular neurosciences. Volume: 46 Issue: 3 Pages: 614-624
  • DOI: 10.1016/j.mcn.2011.01.001
  • Peer Reviewed
• [Presentation] ES 細胞、神経幹細胞への遺伝子導入法 (2012)
  • Author(s): 徳永暁憲
  • Organizer: (口頭発表) 第85回日本生化学会大会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-16
• [Presentation] 神経発生におけるヒストン修飾酵素によるエピジェネティック制御機構の解明 (2012)
  • Author(s): 川上絵理、徳永暁憲、坂本怜子、吉田進昭
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-13
• [Presentation] The role of Polycomb group protein Rybp in neural development (2012)
  • Author(s): 川上絵理、徳永暁憲、坂本怜子、吉田進昭
  • Organizer: 第7回研究所ネットワーク国際シンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2012-06-14
• [Presentation] Analysis of PTB dependent alternative splicing switchduring neural development (2011)
  • Author(s): Akinori TOKUNAGA
  • Organizer: 3rd IMSUT-GCOE Retreat
  • Place of Presentation: Gunma, Japan
  • Year and Date: 2011-03-09
• [Presentation] 初期発生におけるポリコーム群遺伝子rybpの機能解析 (2011)
  • Author(s): 川上絵理、徳永暁憲、坂本怜子、吉田進昭
  • Organizer: 第34回 日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2011-02-14
• [Presentation] 初期発生におけるポリコーム群遺伝子rybpの機能解析 (2011)
  • Author(s): 川上絵理,徳永暁憲,坂本怜子,吉田進昭
  • Organizer: 第3４回 日本分子生物学会
  • Place of Presentation: パシフィコ横浜・横浜・日本
• [Presentation] Analysis of PTB-dependent alternative splicing switch during neural development. (2011)
  • Author(s): Tokunaga A, Shibasaki T, Masaki S, Sakamoto R, Yoshida N.
  • Organizer: The 9th Stem Cell Research Symposium.
  • Place of Presentation: Izumi Garden Gallery・Tokyo・Japan
• [Presentation] RNA結合蛋白PTBは胎生期大脳皮質神経幹細胞において接着結合の維持に重要である (2011)
  • Author(s): 柴嵜 孝幸、徳永 暁憲、坂本 玲子、相良 洋、野口 茂、吉田 進昭
  • Organizer: 第23回 高遠・分子細胞生物学シンポジウム
  • Place of Presentation: 高遠さくらホテル・長野・日本
• [Remarks]
  • URL: http://www.med.oita-u.ac.jp/tenuretrack/researcher/tokunaga.html
• [Remarks] 大分大学若手研究者育成プログラムホームページ
  • URL: http://www.med.oita-u.ac.jp/tenuretrack/researcher/tokunaga.html
• [Remarks]
  • URL: http://www.med.oita-u.ac.jp/tenuretrack/researcher/tokunaga.html